Reproductive Vaccination-
Transcript of Reproductive Vaccination-
Reproductive Vaccination-
Deciphering the MLV
impact on fertility
Decision
•Prebreeding Vaccination of Cattle should• Provide fetal & abortive protection (BVD and
BoHV-1)
• Not impede reproduction
• Impact of MLV vaccine prior to estrus synchronization?
Safety Efficacy
0 10 20 30 40 50 60 70 80 90 100 110 120
C Ranch
O Ranch
W Ranch
S Ranch
Day of Calving Season
Perc
en
tag
e o
f C
alv
es B
orn
Which ranch is likely to be more profitable?
Calving Distribution
Which ranch is better able to take advantage of selling truckload lots?Which ranch is best able to take advantage of early weaning?
0 1 2 3 4 5 6 7 8
9 Months of Gestation
Infertility:
Infection of
ovaries,
interference
with
cyclicity
Sporadic Abortions in Vaccinated Herds
Timeline For IBR and Effects on Reproduction
Spontaneous Abortion
Abortion Storms in Susceptible Herds
Adapted from Youngquist, Current Therapy
in Large Animal Theriogenology, Ch 48, 1997.
Decision
Safety
Efficacy
Phases of Estrous Cycle
Senger, P.L. “Pathways to Pregnancy and Parturition” Current Conceptions Inc. 2nd Edition
Infertility in heifers inoculated with modified-live bovine herpesvirus-1 vaccinal strains against infectious bovine rhinotracheitis on postbreeding day 14
J.M. Miller, DVM PhD; M.J. Van Der Maaten, DVMm PhD: C.A. Whetstone, Ph D
Am J. Vet Res, Vol 50, No. 4, April 1989
• Inocula• Four BHV-1 strains-originated from a repository of expired MLV-1
vaccines against IBR
• Heifers• 10 originated from a herd with no history of vaccination for IBR
• Mated to a seronegative bull by natural service
• Experimental Design• On postbreeding day (PBD) 14
• 2 heifers inoculated IV with 5 ml of 1 of 4 strains of BHV-1 (total of 8 heifers)
• Controls-2 heifers inoculated IV with 5 ml of noninfected cell culture
• Serurm was obtained prior to inoculation to check SN titers• Blood was collected for plasma progesterone at 1 to 3 day
intervals beginning on day of inoculation and continued till PBD 60
Materials and Methods
• BHV-1 was isolated from at least 1 nasal, vaginal swab, and blood sample from each of the 8 heifers inoculated with a BHV-1 vaccinal strain
• Plasma progesterone tests indicated • Control heifers remained pregnant 2 months post breeding
• 4 of 8 inoculated heifers remained pregnant 2 months post breeding
• Pregnancy failure was observed in 4 heifers
• Conclusion• MLV BHV-1 vaccine may result in loss of pregnancy
Results
• 55 healthy excellently managed, confirmed pregnant Angus-cross heifers from the University of Wyoming herd vaccinated at 7-8 months of gestation
• Vaccinated with MLV in May 2010 prebreeding
Case History
• Abortions 32 days post vaccination
• Diagnostics conducted on six of seven aborted fetuses and one heifer that died
• Six heifers confirmed pregnant by ultrasound on vaccination found open at calving
• Lossed 14 pregnancies
Observations
• Diagnostic tests found numerous expressions of IBR symptoms and BoHV-1 antigens present in aborted fetuses
• NO BVDV was detected in aborted fetuses
• Abortions and pregnancy losses among the heifers in this study were observed following the use of a BoHV-1 MLV vaccine
Conclusion
“The effects of vaccination on serum hormone concentrations and conception rates in synchronized naïve beef heifers”
Perry GA, et al., Theriogenology 2012
•59 heifers naïve to BoHV-1 and BVD
•Group 1 (n=21): 2 doses inactivated vaccine* 36 & 8 days prior to AI
•Group 2 (n=7): 1 dose inactivated vaccine* 8 days prior to AI
•Group 3 (n=21): 1 dose MLV vaccine^ 8 days prior to AI
•Group 4 (n=10): 2 doses placebo ̌ 36 & 8 day prior to AI
•All, bred AI and then with bulls 14 days
Materials and methods
*ViraShield® 6+VL5 HB, ̌Inactivated Sterile Water Placebo, Novartis Animal Health US, Inc.
^Bovi-Shield GOLD® FP® 5 VL5, Zoetis Inc.Perry, et al., Theriogenology 2012
•Abnormal estrus cycle (<15 days)
•Plasma P4 concentrations• During the synchronization period
• After AI
•Plasma E2 concentrations
•Pregnancy rates
Measurements
Perry, et al., Theriogenology 2012
•MLV vaccinated heifers had higher % abnormal cycles
•MLV vaccinated heifers had lower E2 concentrations
•Pregnancy rates were lower in heifers that received MLV vaccine
Outcome
Perry, et al., Theriogenology 2012
•Naïve heifers
•Vaccinated inside of time prior to breeding as on label directions
Outcome
• 60 Beef Heifers naïve to BVDV/BoHV-1 with reproductive tract scores ≥ 3 (scale 1-5)
• Heifers randomly assigned to groups and vaccinated 2 days after initial detected estrus:
Animals
Walz et al. Theriogenology 2015
Group Product 1st Vaccination 2nd Vaccination
A (n=20) Express® FP
VL5
2 Days After Detected
Estrus
10 Days Prior to Breeding
B (n=20) Express® FP
VL5
2 Days After Detected
Estrus
31 Days Prior to Breeding
C (n=10) Citadel® VL5 2 Days After Detected
Estrus
10 Days Prior to Breeding
D (n=10) Citadel® VL5 2 Days After Detected
Estrus
31 Days Prior to Breeding
Fig. 1. Experimental design and timeline for vaccine administration, collection of samples, synchronization of estrus, and submission to breeding group. Events occurring after
submission to the breeding group are not included. Group A heifers (n=20) were revaccinated with Express® FP 5 VL5 at 10 days before synchronized natural breeding ((short
prebreeding interval). Group B heifers (n=10) were revaccinated with Express® FP 5 VL5 at 31 days before synchronized natural breeding (long prebreeding interval). Group C
heifers (n=10) were administered Citadel® VL5 at 10 days before synchronized natural breeding (control short prebreeding interval). Group D heifers (n=10) were administered
Citadel® VL5 at 31 days before synchronized natural breeding (control long prebreeding interval). BP,=breeding pen; CIDR-controlled internal drug release; P4=porgesterone.
Walz et al. Theriogenology 2015
• Interestral intervals
• Proportion of heifers exhibiting estrus within 5 days after synchronization
• Serum progesterone & estrogen
• Pregnancy rates
• end of the study
• first 5 days of the breeding season
• Mean day of conception
• Embryonic loss
• Ovarian and conceptus tissues were assayed for BVDV and BoHV-1
Measurements
Walz et al. Theriogenology 2015
Results:Interestral Intervals and Response to Estrus Synchronization
Group First interestrus
interval (days)
Second interestrus
interval (days)
Heifers exhibiting
estrus in first 5 days of
breeding season
Group A 19.2 (n=20) 22.5 (n=19) 19/20 (95%)
Group B 19.1 (n=20) 22.1 (n=20) 17/20 (85%)
Group C 20.0 (n=10) 21.3 (n=10) 9/10 (90%)
Group D 20.1 (n=10) 20.6 (n=10) 9/10 (90%)
p-value P=0.449 P=0.801 P=0.774
Walz et al. Theriogenology 2015
Results:Interestral Intervals and Response to Estrus Synchronization
Group First interestrus
interval (days)
Second interestrus
interval (days)
Heifers exhibiting
estrus in first 5 days of
breeding season
Group A 19.2 (n=20) 22.5 (n=19) 19/20 (95%)
Group B 19.1 (n=20) 22.1 (n=20) 17/20 (85%)
Group C 20.0 (n=10) 21.3 (n=10) 9/10 (90%)
Group D 20.1 (n=10) 20.6 (n=10) 9/10 (90%)
p-value P=0.449 P=0.801 P=0.774
Vaccination with Express® FP 5-VL5 did not
result in negative reproductive impact based on:
• Duration of 1st or 2nd interestrus intervals
• Proportion of heifers exhibiting estrus
within 5 days of synchronization
• Mean day of conception
• Pregnancies resulting from the first five
days of the breeding season
Walz et al. Theriogenology 2015
Results:Pregnancy Rates and Mean Day of Conception Within Breeding Season
Group Embryonic loss
detected prior to
study end date
Pregnant at study
end date
Pregnant at study
end from first 5
days of breeding
season
Mean day of
conception within
breeding season
Group A 2/20 (10%) 14/20 (70%) 12/20
(60%)
4.2
Group B 1/20 (5%) 17/20 (85%) 15/20
(75%)
3.1
Group C 1/10 (10%) 9/10 (90%) 6/10 (60%) 5.3
Group D 0/10 (0%) 10/10
(100%)
5/10 (50%) 6.3
p-value P=0.72 P=0.177 P=0.556 P=0.459
Walz et al. Theriogenology 2015
Results:Pregnancy Rates and Mean Day of Conception Within Breeding Season
Group Embryonic loss
detected prior to
study end date
Pregnant at study
end date
Pregnant at study
end from first 5
days of breeding
season
Mean day of
conception within
breeding season
Group A 2/20 (10%) 14/20 (70%) 12/20
(60%)
4.2
Group B 1/20 (5%) 17/20 (85%) 15/20
(75%)
3.1
Group C 1/10 (10%) 9/10 (90%) 6/10 (60%) 5.3
Group D 0/10 (0%) 10/10
(100%)
5/10 (50%) 6.3
p-value P=0.72 P=0.177 P=0.556 P=0.459
Vaccination with Express® FP 5-VL5 did
not result in negative reproductive impact
based on:
• Embryonic loss detected prior to the
end of the study
• Pregnancy rates at the end of the
study
Walz et al. Theriogenology 2015
•Vaccination with Express® FP 5-VL5 did not result in negative reproductive impact based on:
• Serum progesterone concentrations during estrus and diestrus
• Serum estrogen concentrations following initial vaccination or in the breeding pen
• BVDV was not detected in luteal tissue, ovarian tissue, or fetal tissues
• BoHV-1 was not detected in luteal tissue, ovarian tissue, or fetal tissues
Results
Walz et al. Theriogenology 2015
First Service Conception Rates
Following Vaccination with
Express® FP 5
C. Jones, K. Haden, D. Robbins
BIVI Tech Bulletin 03-106R-1
Effect of Vaccination on First Service Conception Rates
Study conducted in a commercial
cow/calf operation that was on a
routine MLV vaccination program.
• First Service Conception Rates Following Vaccination with Breed-Back FP 5 (Express FP 5) Vaccine
• Previous studies
• Vaccination of sero-negative cows with MLV vaccine just prior to breeding, may reduce fertility
• This has impacted pre-breeding vaccination practices in beef and dairy cows.
Rationale for Study
• Modified live IBR and BVD are commonly used to vaccinate cows prior to breeding
• An immune response is stimulated following replication of the modified live viruses
• There is a concern that the replicating viruses may invade the ovary, interfere with ovarian function, and result in infertility
Background
• Grooms DL, et al. J Vet Diagn Invest 1998; 10:130-134.• Isolated BVD virus from ovaries of sero-negative heifers
on day 12 following vaccination with MLV• Showed presence of BVD antigen in the ovaries of sero-
negative cows 30 days post-vaccination with MLV
• Chiang BC, et al. Theriogeniology 1990; 33:1113-1120.• Reduction in conception rate when sero-negative heifers
were vaccinated with a modified live IBR just prior to turning with bulls.
Background (continued)
• To evaluate if Express® FP 5 administered 10 days prior to breeding will reduce first service conception rates and overall pregnancy rates in cows that had been vaccinated with a modified live IBR and BVD vaccine prior to previous breeding seasons.
Objective
• 191 cows were sorted into two groups based on age and days post-calving
• All cows were 2 years of age
• All cows had received at least two MLV vaccines as heifers and had been vaccinated with MLV vaccine prior to each of the previous breeding seasons
• All were synchronized with the 7-11 Synch program and were time bred 60 hours following the second prostaglandin injection
Protocol
Treatment Groups
N Vaccination Timing Vaccines
Group 1 96 4 weeks prior to AI
Express® FP 5
Vibrio-Lepto-5
Group 2 95 10 days prior to AI
Express® FP 5
Vibrio-Lepto-5
MGA .5mg/hd/d
28 Days
10 Days
Vaccination and Synchronization Timeline
Group 1
Vaccinated
Sto
p M
GA
Start
MGAGnRH
Group 2
Vaccinated
2n
d
PG
F 2ά
GnRH
and A.I.
8 Days 7 Days 1 Day 3 Days 7 Days 60 hours
1st
PG
F 2ά
All cows were fed MGA and injected with PGF2ά and GnRH.
• Bulls were turned with cows six days following AI.
• All cows were pregnancy checked using ultrasound 33 days after AI.
• Cows open 33 days following AI were pregnancy checked via ultrasound 35 days after removal of bulls.
Protocol (continued)
Results
First Service Conception Rate
# Pregnant # Open Total % Pregnanta
Group 1 51 45 96 53.1%
Group 2 49 45 94b 52.1%
aNo significant difference between groups 1 and 2 (p>.05).bOne cow culled prior to pregnancy check.
Note: The first service conception rates were consistent with previous
years in which the same synchronization and fixed-time breeding
program were used in this herd.
Results
Overall Pregnancy Rate
# Pregnant # Open Total % Pregnanta
Group 1 92 4 96 95.8%
Group 2 87 7 94 92.5%
aNo significant difference between groups 1 and 2 (p>.05).
• The first service conception rate and overall pregnancy rate were not significantly different in cows vaccinated with Express® FP 5 ten days prior to artificial insemination versus cows vaccinated four weeks prior to artificial insemination.
• Cows utilized in this study had received a yearly pre-breeding MLV vaccine in the years prior to the study.
Summary
Decision Safety
Efficacy
Timeline of BVDV Effects on Reproduction
0 1 2 3 4 5 6 7 8 9
Months of Gestation
Persistent Infection
Adapted from Grooms, 2004
EED
Abortion
Congenital Defects
Congenital Infections (
Cl)
INFERTILITY
• Prevention of persistent infection caused by BVDV Type 1 (including 1b) & Type 2
• 4 different non-cytopathic BVDV challenge viruses
• 2 BVDV Type 1b
• 2 BVDV Type 2
• 7 different challenge studies
Express® FP Vaccines PreventBVDV Persistent Infection
Challenge
Virus
Treatment
Group
# Positive/
Total
Total %
Protected
BVDV Type
1b
(3 Studies)
Vaccinates
Controls
2 of 51
38 of 41
96%
7%
BVDV Type 2
(4 Studies)
Vaccinates
Controls
2 of 64
50 of 51
97%
2%
Summary of All BVDV Label Studies
• First vaccine labeled for prevention of persistently infected calves
• First vaccine with written financial guarantee
Express® FP Vaccines
Challenge Virus Treatment Group PI Positive
BVDV Type 1b Vaccinates
Controls
1/22 (4.5%)
20/23 (87.0%)
BVDV Type 2 Vaccinates
Controls
0/18 (0%)
21/22 (95.5%)
Protection Against Persistent Infection1 Year After Vaccination
A single dose of Express® FP 5-VL5 administered one
year prior to challenge with BVDV Type 1b or Type 2:• Demonstrated fetal protection against persistent infection
Zimmerman A., et al, The Bovine Practitioner 47, 1 (2013)
Challenge
Virus
Treatment
Group
Abortions
Cooper IBR Controls 18/19 (94.7%)
Cooper IBR Vaccinated 12
months
2/13
(15.4%)
p<0.0001
IBR Abortion Challenge
A single dose of Express® FP 5-VL5 administered one
year prior to challenge with IBR Cooper Strain:• Demonstrated protection against IBR abortion for 12 months
Zimmerman A., et al, The Bovine Practitioner 47, 2 (2013)
Decision
Safety Efficacy
• IBR vaccination of pregnant cows & heifers is
potentially the highest risk of causing abortions.
• Modified live IBR vaccine should be given to heifers
at least 30 days prior to breeding.
• If heifers are not properly vaccinated they should not
be vaccinated with MLV vaccines during pregnancy
Conclusion
When designing heifer, pre-breeding
vaccination programs, vaccination history
should be carefully considered and multivalent
MLV vaccines should be used according to
label directions.
Decision
Safety Efficacy
• IBR vaccination of pregnant cows & heifers is
potentially the highest risk of causing abortions.
• Modified live IBR vaccine should be given to heifers
at least 30 days prior to breeding.
• If heifers are not properly vaccinated they should not
be vaccinated with MLV vaccines during pregnancy
Decision
Safety Efficacy
• IBR vaccination of pregnant cows & heifers is
potentially the highest risk of causing abortions.
• Modified live IBR vaccine should be given to heifers
at least 30 days prior to breeding.
• If heifers are not properly vaccinated they should not
be vaccinated with MLV vaccines during pregnancy
Conclusion
When designing heifer, pre-breeding
vaccination programs, vaccination history
should be carefully considered and multivalent
MLV vaccines should be used according to
label directions.
Thank you!
Final questions?